Integration site distributions from pre- and postinfusion time points in or near transcription units, highly expressed genes, and cancer-associated genes. (A) Proportion of integration sites found within genes as defined by the RefSeq database normalized to the proportion of matched random control sites within genes. The line at 1 marks the expected frequency for a random distribution; levels above 1 indicate associations enriched or favored compared with random; below 1, disfavored. Ex vivo indicates integration sites from patient cells transduced ex vivo, before infusion back into the patient; Jurkat, sites from Jurkat cells infected in vitro; postinfusion, sites isolated from CD4 T cells taken postinfusion (supplemental Table 8). Ex vivo and postinfusion datasets represent pooled sites from all 5 patients and time points. (B) Proportion of sites in highly expressed genes. Genes were binned into 7 equal bins of increasing gene expression as measured by the Affymetrix HU133 plus Version 2.0 gene chip array. Genomic intervals of 1 Mb were annotated for the numbers of highly expressed genes, with low expression on the left and high expression on the right, and then the proportions of integration sites in these bins were plotted. The line at 1 shows the expectation for a random distribution. “Ex vivo” and “postinfusion” represent pooled data from all 5 patients. (C) Proportion of sites near cancer-associated genes. The plot shows the proportion of sites < 50 kb from a RefSeq gene that were also < 50 kb from a cancer-associated gene. No patient showed significant enrichment of integration sites near cancer-associated genes (Fisher exact test, 1-sided in the direction of enrichment postinfusion found no pairs significantly different).